Much of our knowledge about the neuronal organization of the cerebral cortex comes from studies of principal neurons. Only very recent works point to the critical role of inhibitory interneurons in the regulation of the complex interactions of principal cells, including population oscillations, plasticity, epileptic synchronization, hormonal effects and cortical development. There are several groups of hippocampal inhibitory cells with different properties and hypothesized functions. The goal of the project is to reveal the relationship between biochemical, afferent and target properties of hippocampal interneurons and their physiological function in the regulation of hippocampal networks. Intracellular labeling in vivo and in vitro will be used in order to compare physiological properties with the morphological and biochemical features of inhibitory cells. Recordings will be made from interneuron-principal cell pairs to examine synaptic inhibition mediated by dendritic and perisomatic contacts and to identify cells that activate GABA-A and GABA-B receptors. In in vivo experiments the discharge properties of interneurons will be correlated with behaviorally relevant population patterns. The whole axonal arbor of the interneurons will be reconstructed and their principal cell and other interneuronal targets will be quantitatively determined by light and electron microscopic methods. The peptide or calcium binding protein content of the recorded interneurons will be determined by double labeling techniques. The physiological actions of septohippocampal cholinergic and GABAergic afferents on hippocampal inhibitory cell excitability and on GABA release from inhibitory terminals will be investigated in a novel septohippocampal slice preparation. The findings will reveal the physiological function of different subclasses of interneurons, including a) timing of action potentials in spatially distinct principal cell populations, b) behavior-dependent control of afferent and intrahippocampal pathways and c) segregation of plasticity and neuronal transmission. Such knowledge is essential for understanding the consequences of interneuronal damage in disease.